Endocrine Abstracts (2017) 49 GP186 | DOI: 10.1530/endoabs.49.GP186

24 hour urinary 5-hydroxyindoleacetic acid (5-HIAA) doubling-time (DT) is associated with disease-specific mortality (DSM) and progression-free survival (PFS) in patients with neuroendocrine tumors (NETs)

Amit Tirosh1,2, Naris Nilubol3, Dhaval Patel3 & Electron Kebebew3

1National Institutes of Health, Bethesda, Maryland, USA; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Endocrine Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Background: Biochemical biomarker DT is used clinically for prognosis prediction in several solid malignancies. The aim of the current analysis was to determine whether biomarker DT has any prognostic utility in patients with NETs.

Methods: Patients with NETs (n=184) were enrolled in a prospective study with comprehensive biochemical analysis. The current analysis included subjects with increasing 5-HIAA levels in at least two consecutive measurements. DTs for each biomarker were calculated using the formula DT = [log10(2)*(time interval between tests)]/[log10(2nd value)–log10(1st value)]. Log-rank test was used to assess differences in DSM or PFS risk by DT. The c-statistic of 5-HIAA predictive utility for DSM was calculated using receiver operating characteristic (ROC) curve analysis. DSM and PFS were compared by 5-HIAA DT using Kaplan-Meier survival analysis and multivariate analysis was performed using Cox regression.

Results: 91 patients had increasing 5-HIAA levels. Four patients died during a median follow-up of 8 months (interquartile range, 12). The c-statistic for DSM prediction by 5-HIAA was 0.76 (95% CI 0.62–0.90), and 5-HIAA DT <434 days had positive and negative predictive values for DSM of 75 and 76%, respectively. Patients with a 5-HIAA DT <434 days had higher risk for DSM during follow-up (Log-Rank test, P=0.02). In sub-group analysis this difference was found only among patients with a non-pancreatic NET (P=0.002). In the entire cohort, PFS were comparable between patients with 5-HIAA DT longer vs. shorter than 434 days. However, patients with small-intestine NET with 5-HIAA DT <434 days had a higher risk for progression (P=0.006), also in multivariate analysis (Hazard Ratio 15.3, 95% CI 1.01–232.6, P=0.049).

Conclusions: Short 5-HIAA DT is associated with increased DSM and lower PFS in patients with NET, and specifically among those with SINET, and can be used as a prognostic measure in NET patients.

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